During proton therapy treatment, protons interact with both the nucleus and bound electrons of atoms within patient tissue. Proton-nucleus interactions can leave behind an intact atomic nucleus in an excited energy state that quickly decays, frequently through emission of a characteristic gamma-ray, a phenomenon known as "prompt emission". This gamma emission occurs only where proton-nucleus interactions (and thus dose deposition) occur and the energy spectrum of the emission is dependent on the specific atomic composition of the irradiated tissue. We hypothesize that by properly measuring the prompt gamma-ray emission that occurs during proton dose delivery, the dose delivery and the composition of tissue irradiated can be verified. The long term goal of this research is to develop a clinically viable Prompt Gamma Imaging (PGI) system capable of measuring both the composition and density of tissues irradiated within the patient. The specific aims of this proposal are (1) to determine the response of gamma-ray detectors within a proton treatment vault and (2) to determine the inherent resolution of image reconstruction for the proposed PGI method. To achieve the stated aims, both measurements and Monte Carlo calculations will be made to determine the shielding levels and detector timing response required to isolate and measure prompt emission during proton beam delivery. Calculations of the prompt emission detection process from a Monte Carlo model will be used to determine the effects of the finite energy and spatial resolution of the gamma-ray detectors on the resolution of images reconstructed with the proposed PGI method. Based on the results of these studies, we will determine the overall feasibility of measuring the prompt gamma-ray spectra emitted during proton beam radiotherapy and for reconstructing images of the composition and density of tissues irradiated with the proposed PGI method. The significance of a method to image and track changes to the elemental composition and densities of tissues irradiated during proton therapy is multi-fold. First, such a method could allow for the direct measurement of changes to the stopping powers for irradiated tissues over the course of treatment. The stopping power values obtained from measurements would allow for more accurate calculation of proton beam range and dose delivery within the patient over the course of treatment, thus improving accuracy of the proton treatment delivery. Second, PGI would provide a direct method to evaluate changes in irradiated tissues, such as tumor hypoxia or the elemental composition of healthy tissues over the treatment course that could be correlated to tumor response and/or the onset of normal tissue complications. PUBLIC HEALTH RELEVANCE: The proposed research aims to develop novel methods to measure and image the atomic composition of tissues irradiated during proton radiotherapy in-vivo, allowing us to study biological changes and response of these tissues. This would provide a means to measure and track changes to elemental composition in these tissues on a daily basis over the course of treatment. Such capabilities would allow for the monitoring of a patient's response to proton radiotherapy (via measured changes to tissue composition), thus providing a means for the oncologists to change and adapt treatment delivery for each patient individually based on their measured response.